Technical challenges and limitations of current mouse models of ovarian cancerReport as inadecuate




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Journal of Ovarian Research

, 5:39

First Online: 29 November 2012Received: 16 October 2012Accepted: 22 November 2012

Abstract

The development of genetically engineered models GEM of epithelial ovarian cancer EOC has been very successful, with well validated models representing high grade and low grade serous adenocarcinomas and endometrioid carcinoma EC. Most of these models were developed using technologies intended to target the ovarian surface epithelium OSE, the cell type long believed to be the origin of EOC. More recent evidence has highlighted what is likely a more prevalent role of the secretory cell of the fallopian tube in the ontogeny of EOC, however none of the GEM of EOC have demonstrated successful targeting of this important cell type.

The precise technologies exploited to develop the existing GEM of EOC are varied and carry with them advantages and disadvantages. The use of tissue specific promoters to model disease has been very successful, but the lack of any truly specific OSE or oviductal secretory cell promoters makes the outcomes of these models quite unpredictable. Effecting genetic change by the administration of adenoviral vectors expressing Cre recombinase may alleviate the perceived need for tissue specific promoters, however the efficiencies of infection of different cell types is subject to numerous biological parameters that may lead to preferential targeting of certain cell populations.

One important future avenue of GEM of EOC is the evaluation of the role of genetic modifiers. We have found that genetic background can lead to contrasting phenotypes in one model of ovarian cancer, and data from other laboratories have also hinted that the exact genetic background of the model may influence the resulting phenotype. The different genetic backgrounds may modify the biology of the tumors in a manner that will be relevant to human disease, but they may also be modifying parameters which impact the response of the host to the technologies employed to develop the model.

KeywordsOvarian cancer Mouse models Genetically engineered Ovary Oviduct Ovarian surface epithelium AbbreviationsAmhAnti-Müllerian hormone

Amhr2Anti-Müllerian hormone type 2 receptor

ECEndometrioid carcinoma

FshrFollicle stimulating hormone receptor

HGSCHigh grade serous carcinoma

LacZβ-galactosidase

LGSCLow grade serous carcinoma

LMSleiomyosarcoma

MISIIRMüllerian inhibiting substance type 2 receptor

Ovgp1oviduct specific glycoprotein

OSEOvarian surface epithelium

SV40TAgSV40 early region

TAgSV40 large T antigen.

Electronic supplementary materialThe online version of this article doi:10.1186-1757-2215-5-39 contains supplementary material, which is available to authorized users.

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Author: Kenneth Garson - Lisa F Gamwell - Elizabeth MG Pitre - Barbara C Vanderhyden

Source: https://link.springer.com/







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